Nigella sativa L.

Last updated: 15 November 2016

Scientific Name

Nigella sativa L.

Synonyms

Nigella cretica Mill. [1]

Vernacular Name

Malaysia Jintan hitam [2]
English Black cumin, small fennel, love-in-a-mist [2]
China Zai pei hei zhong cao, Hei xian hao [2]
India Kalonji [2]
Indonesia Jinten hitam [2]
Saudi Arabia Habbah Albarakah [2]
France Cumin noir, nigelle cultivée, toute-épice [2]

Geographical Distributions

Nigella sativa is probably indigenous to the Mediterranean region and the Middle East up to India. It has long been cultivated and is mentioned in ancient Hebrew, Greek and Roman texts. It is cultivated in the subtropical belt extending from Morocco to northern India and Bangladesh, in East Africa and in the former Soviet Union. In Europe, North America and Southeast Asia, it is cultivated on a minor scale mainly for medicinal purposes. [2]

Botanical Description

N. sativa is a member of Ranunculaceae family. N. sativa is an erect annual herb, up to 70 cm tall, with a well-developed yellow-brown taproot and numerous feeder roots. The stem is profusely branched, subterete, ribbed, and sometimes hollow when old and light to dark green. [2]

The leaves are arranged alternately. The stipules are absent. The petiole is strongly broadened at the base, light green, only present in basal leaves, measures 1-6 cm long, ribbed and minutely hairy. The leaf measures up to 7 cm x 5 cm in outline, bi-,tri- or even multi-pinnately dissected into short, thin sublinear, divergent, slightly pilose lobes, which are normally green but sometimes turn reddish brown. [2]

The flowers are terminal and solitary. The pedicel is (2-)4-8(-11) mm long, minutely hairy and ribbed. All parts of the flower are inserted on a pale yellow, fleshy, depressed-conical receptacle, measuring about 2 mm in diametre and visible as an orange-brown ring below the carpels in fruit. There are 5 sepals which are petal-like, ovate, measuring 13-17 mm x 6-12 mm, obtuse at apex, basally tapering into a claw 2-3 mm long and papillose to pilose. The sepal is pale green when young but sometimes partly reddish while the inside is pale blue-white when becoming older. There are (6-)8(-11) petals which are with short claw, 2-lobed blade, with lobes enclosing the nectar pocket, with dorsal lobe measuring 3.5-5.5 mm x 2.5-4.5 mm, with bifid apex, greenish-white with violet lines, with oblong ventral lobe, measuring 2.5-4 mm long, violet at the base and white at the apex. The stamens are in (6-)8(-10) groups with 3-7 stamens each. The filaments are 3-9 mm long, linear, violet-blue to pale blue and with yellow anthers. The pistil is lobed and composed of 3-7 white-granular carpels. It is almost connate at the base and forms a compound ovary, which is 4-9 mm long with free stigmas. [2]

The fruit is a ribbed, oblongoid, tuberculate capsule, measuring 6-16 mm x 5-12 mm, greyish-green to brown at maturity, many-seeded and with persistent stigmas. [2]

The seed is 3(-4)-sided, obpyramidal measuring 3 mm x 1.5-2 mm, wrinkled-tuberculate, dark black and with a carrot-like smell. Its embryo is minute, embedded in copious and fatty endosperm. [2]

Cultivation

N. sativa is a hardy crop and can grow under a wide range of temperatures from 5-25°C, the optimum being about 14°C. In Ethiopia, it is cultivated as a rainfed crop in the highlands at 1500-2500 m altitude. It is successfully grown in most kinds of soil with pH 5-8. [2]

Chemical Constituent

The seeds of N. sativa have been reported to contain 20.85% protein, 38.20% fat, 4.64% moisture, 4.37% ash, 7.94% crude fibre and 31.94% total carbohydrate. [3] No trace of lead, cadmium and arsenic were found in the seeds. The predominant elements present were potassium, phosphorus, sodium and iron while zinc, calcium, magnesium, manganese and copper were found at lower levels. [3] The seeds may potentially be an important nutritional source as the content of essential amino acids contributes to about 30% of the total protein content while about 84% of the fatty acids is composed of unsaturated fatty acids, predominantly linoleic and oleic acids. [3][4]

Oil extracts of the seeds also contain significant amounts of sterols. β-Sitosterol was the dominant sterol (69%); while campesterol and stigmasterol constitute 12% and 19%, respectively of the total sterols. [4] The seed oil was found to be rich in polyphenols (1,744 µg/g) and tocopherols (340 µg/g of total a-,b- and g-isomers). [4]

N. sativa seed has been reported to contain 36%-38% fixed oils, proteins, alkaloids, saponins and 0.4%-2.5% essential oil [5]. The fixed oil is composed mainly of fatty acids, namely, linoleic (C18:2), oleic (C18:1) and palmitic acids (C16:0). [3][6][7][8][9] Many components were characterized from the essential oil, but the major ones were thymoquinone (27.8%-57.0%), ρ-cymene (7.1%-15.5%), carvacrol (5.8%-11.6%), t-anethole (0.25%-2.3%), 4-terpineol (2.0%-6.6%) and longifoline (1.0%-8.0%). [5][10] Thymoquinone is the main active constituent of the volatile oil extracted from N. sativa. [5][11][12] Good quality control methods were used for quantifying the pharmacological actives thymoquinone, dithymoquinone, thymohydroquinone and thymol, in both the seed oils and extracts of N. sativa. [13]

N. sativa seed has been reported to contain nigellone, which was isolated from the volatile oil fraction and nigellidine which contains an indazole nucleus. [14][15] N. sativa seed has been reported to contain three flavonoid glycosides and triterpene saponins. [16][17]

Plant Part Used

Seeds [2]

Traditional Use

The seeds, on account of their aromatic nature, are used as a spice in cooking, particularly in Italy, Germany, Southern France and Asia. In folk medicine, it is used by the Egyptian public as a diuretic and carminative, while the expressed oil is used in the treatment of asthma, respiratory oppression and coughs. [14]

Black cumin oil is found in the foods and beverage industry as a flavouring agent, particularly in Indian and Middle Eastern products. It is also found in alcoholic beverages. It is less often used in the fragrance industry, but is found in some body care products. In therapeutic aromatherapy, it is used as single oil and in more complex formulations. The steam-distilled oil of black cumin is thin and clear to yellowish in color. It has a spicy bitter and very pungent aroma. [2]

Preclinical Data

Pharmacology

Antimicrobial and antidermatophyte activity

The ethanolic extract of N. sativa was shown to have outstanding in vitro antibacterial activity against methicillin resistant and sensitive strains of Staphylococcus aureus. [18] Microgram concentrations of the diethyl ether extract of N. sativa (25-400 μg extract/disc) inhibited growth of Gram-positive bacteria (S. aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and a pathogenic yeast (Candida albicans). [19] Salmonella thyphimurium was non-sensitive to the range of concentrations of the extract used in the study (25-400 μg/disc). The extract showed antibacterial synergism with streptomycin and gentamycin. In vivo studies showed that the diethyl ether extract successfully eradicated localized infections of S. aureus in mice. [19] N. sativa oil may potentially be useful for inhibition of Listeria monocytogenes in food as it showed strong antibacterial activity against 20 strains of the bacteria with the oil producing inhibition zones that were significantly larger than that of gentamicin. [20]

N. sativa elicited antiviral effect against murine cytomegalovirus (MCMV). [21] It was suggested that the effect against MCMV infection may be mediated by an increase in macrophage number and function, and IFN-γ production. [21]

N. sativa is a potential source for antidermatophyte drugs. The ether extract of the seed and its active principle, thymoquinone produced minimum inhibitory concentrations (MICs) of 10-40 and 0.125-0.25 mg/ml, respectively against 8 species of dermatophytes (4 species of Trichophyton rubrum, each species of T. interdigitale, T. mentagrophytes, Epidermophyton floccosum and Microsporum canis). In contrast, the MICs for griseofulvin ranged from 0.00095 to 0.0155 mg/ml. This supports its use in folk medicine for the treatment of fungal skin infections. [22] N. sativa extract and thymoquinone showed protection against chromosomal aberrations in mouse cells infected with schistosomiasis. [23] In Schistosomiasis mansoni infected mice, N. sativa oil (2.5 and 5 mL/kg, orally for 2 weeks) either given alone or with praziquantel was able to reduce the number of worms in the liver and the total number of ova deposited in the liver and intestine. [24] There was also an increase in the number of dead ova and a reduction in the granuloma diameters and partial protection against S. mansoni–induced increases in serum activities of L-alanine aminotransferease (ALT), g-glutamyl transferase (GGT) and alkaline phosphatase (AP) and S. mansoni–induced decrease in serum albumin. [24] N. sativa crushed seeds showed strong biocidal effects against all stages of S. mansoni namely, the miracidia, cercaria and adult worms and also inhibited egg-laying of adult female worms. [25] These effects were probably mediated by the crushed seeds inducing a state of oxidative stress in the worms [25] and/or through modulation of the immune response as was observed in S. mansoni infected mice. [26]

Antioxidant activity

The antioxidant activity of N. sativa oil extracted using supercritical CO2 as the solvent was dependent on thymoquinone and carvacrol but was only 0.14 of the activity of a-tocopherol. [27] The antioxidant potency of a methanolic extract of N. sativa was found to be higher than the aqueous extract in soybean lipoxygenase and rat liver microsomal lipid peroxidation assays, and also in the DPPH assay. [28] The phenolic content in both the methanolic and aqueous extracts was about 4.1 mg/g. [28] Antioxidants present in N. sativa seeds include selenium, DL-a- and DL-g-tocopherol, all-trans retinol, thymoquinone and thymol with mean concentrations of 0.17, 9.02, 5.42, 0.27, 2224.5 and 169.4 mg/kg fresh weight, respectively. [29] N. sativa and thymoquinone partly protected rat gastric mucosa from acute ethanol-induced gastric mucosal damage, with the gastroprotection mediated by their antiperoxidative, antioxidant and antihistaminic effects. [30] Supplementation of the diet of rats fed oxidised corn oil with N. sativa led to an improvement in the overall antioxidant capacity as evidenced by a marked reduction in red blood cell hemolysis and plasma AST/ALT activities and a reduction in the formation of thiobarbituric acid reactive substances, indices of peroxiddative damage. [31] The antioxidant effects are attributed to thymoquinone, a main constituent of the volatile oil of N. sativa. [32] Thymoquinone inhibited iron-dependent microsomal lipid peroxidation with an IC50 of 16.8 µM and is a potent superoxide anion scavenger with IC50of 3.35 µM but did not cause DNA damage in the bleomycin Fe(III) system. [32] Rats pretreated with thymoquinone (100 mg/kg orally) or commercial bloack seed oil (100 µL/kg orally) for 30 min and for 1 week were protected against methionine induced-hyperhomocysteinemia and its associated state of oxidative stress when measured at 5 hours after the methionine load. [33]

Hepatoprotective activity

The hepatoprotective activity of thymoquinone was compared to silybin, a known hepatoprotective agent. Although thymoquinone protected against liver enzymes leakage, the degree of protection was less than that of by silybin. [11]

Analgesic and antiinflammatory activity

The aqueous and methanolic extracts of N. sativa (dose equivalent to 1.25 g dried plant/kg weight) showed analgesic effect in mice as it produced significant increases in reaction times in the hot plate and pressure tests. [34][35] Both extracts elicited depressant activity on exploratory conduct and reduced spontaneous motility in mice without causing failure of motor coordination. Both extracts also reduced the normal body temperature. [35]

The aqueous extract also has an anti-inflammatory effect as demonstrated by its inhibitory effects on carrageenan-induced paw edema in mice. [34] In rat models of acute lung injury or acute respiratory distress syndrome, thymoquinone (6 mg/kg, administered intraperitoneally) was able to improve lung oxygenation while its co-administration with steroids (thymoquinone 6 mg/kg plus methylprednisolone 10 mg/kg, intraperitoneally) protected lung tissue from the hazardous effects of intratracheal instillation of human gastric juice (pH 1.2). [36] The anti-inflammatory effects of thymoquinone was supported by its ability to attenuate allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the airways and goblet cell hyperplasia. [12][37] Attenuation of airway inflammation occurred concomitant to inhibition of COX-2 (cyclogenase) protein expression and prostaglandin D2 production in a mouse model of allergic airway inflammation induced with ovalbumin. [37]

Aqueous and macerated extracts of N. sativa produced relaxant, anticholinergic (functional antagonism) and antihistaminic effects on guinea pig tracheal chains. [38] The relaxant effect of the extracts, however, was probably not associated with the calcium channel blocking effect of the herb as the extracts did not inhibit KCl-induced contraction of tracheal chains. [38]

Antitumour activity

The biological activities of N. sativa seeds were recently reviewed. [39] Besides the activities mentioned above, the oil and seed constituents of N. sativa showed antitumour effects in vitro and in vivo. [39][40] N. sativa (50 and 100 mg/kg body weight, orally) given prophylactically to potassium bromate-treated rats elicited potent chemopreventive effects as evidenced by the suppression of hyperproliferative response, renal oxidative stress and toxicity. [41] N. sativa also protected against ferric nitrilotriacetate (Fe-NTA)-induced oxidative stress, hyperproliferative response and renal carcinogenesis in rats. [42] The active principle of N. sativa seeds exhibited 50% cytotoxicity to Ehrlich ascites carcinoma, Dalton’s lymphoma ascites and Sarcoma-180 cells at concentrations of 1.5, 3 and 1.5 μg/mL, respectively, with little activity against lymphocytes. [43] The ethyl acetate fraction of N. sativa seed showed cytotoxicity against cancer cell lines, viz, P388, Molt4, Wehi 164, LL/2, Hep G2, SW620 and J82 as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-phenyltetrazolium bromide (MTT) assay. [44] The anti-tumor effects of N. sativa oil was attributed to the volatile oil obtained from the seed, the major active components of which were thymoquinone and dithymoquinone. [44][45] Thymoquinone killed cancer cells by a process that involved apoptosis and cell cycle arrest with little effect in non-cancerous cells. [46]

Diethylnitrosamine-induced hepatocarcinogenesis was instituted in rats. Ten weeks of feeding of these rats with a decoction made of N. sativa seeds, Smilax glabra rhizome and Hemidesmus indicus root bark (at doses of 4 or 6 g/kg body weight/day, orally) resulted their protection as evidenced by inhibition in the early phase of the carcinogenesis. [47][48]

N. sativa decreased the frequency of mammary carcinoma in rats. This was associated with decreased levels of markers of tumorigenicity, endocrine derangement oxidative stress and increased apoptotic activity. [49]

Anticonvulsant activity

Thymoquinone may have anticonvulsant activity in petit mal epilepsy probably through an opoid receptor-mediated increase in GABAergic tone. [50] The use of N. sativa oil could be a potential approach for arresting or inhibiting seizure genesis caused by excitotoxic agents. [51]

Immunomodulatory activity

N. sativa does not seem to have immunomodulatory effect on T-helper 1 and T-helper 2 cells in response to allergen stimulation. [52] However, the extract inhibited human neutrophil elastase activity which was mainly attributed to carvacrol. [53]

Hematological activity

A methanolic extract of N. sativa showed inhibitory effects on arachidonic acid-induced platelet aggregation and on blood coagulation. [54] The extracts appear to induce transient changes in the coagulation activity of rats. [55] N. sativa may have a beneficial role as a hypoglycaemic agent with protective effects against pancreatic β-cell damage from alloxan-induced diabetes in rats by virtue of its ability to decrease oxidative stress and to preserve pancreatic β-cell integrity. [56] The treatment of alloxan-induced diabetic rabbits with N. sativa resulted in lowering of elevated glucose concentrations, and an increase in the lowered serum triiodothyronine concentration. [57] N. sativa also increased the depressed red and white blood cells count, the packed cell volume and neutrophil percentage but decreased the elevated heart rate in the alloxan-induced diabetic rabbits. [58]

N. sativa oil may also play a role in modulating the balance of fibrinolysis/thrombus formation by modulating the fibrinolytic potential of endothelial cells. [59][60]

Gastric secretion activity

N. sativa extract was proven to have a protective action against ethanol- induced ulcer in rats. [61]

Antidiabetes activity

A study used short-circuit technique and was reported to show a dose-dependent glucose tolerance that is as efficient as Metformin drug with ability to reduce weight of the rats at 2g/kg per day dose. [62] A combination of N. sativa and human parathyroid hormone consumed by rats with diabetes for 4 weeks reported to have significant insulin-immunoreactivity decreasing the glucose availability. [63]

Antiasthmatic activity

Boiled extracts of N. sativa when compared with theophylline at respective doses using pulmonary function tests reported significant improvement in the expiratory flow which is comparable to theophylline and salbutamol during onset treatment only. [64]

Pulmonary protective activity

A study reported that rats with lung injury due to foreign materials into the trachea and lungs was treated with N. sativa for 7 days and significant results was shown relating to pulmonary investigations such as decrease in peribronchial inflammatory cell infiltration. [65]

 

Toxicity

The fixed oil of N. sativa seeds has low toxicity in mice and rats. [66]  This suggests that therapeutic doses of the fixed oil of N. sativa has a wide margin of safety, however, this does not take into account the changes in haemoglobin metabolism and the fall of leucocytes and platelet counts. [66]

The acute toxicity of thymoquinone is very low (LD50: 2.4 g/kg with 95% C.L. (1.52–3.77)) in mice. The maximum non-fatal dose was 500 mg/kg which is approximately 12 times the anticonvulsive dose of 40 mg/kg.  It is generally well tolerated when given subchronically in drinking water at doses of 30, 60, and 90 mg/kg/day. Hypoglycemia was the only effect associated with the subchronic administration of thymoquinone. [67]

The toxicity of N. sativa fixed oil extract is as follows: LD1=0.057 mL/kg, LD10=0.157 mL/kg, LD50=0.542 mL/kg, LD90=1.866 mL/kg, LD99=5.111 mL/kg. [68]

In addition, when N. sativa is administered with gentamicin sulphate, the anti-bacterial toxicity is reduced significantly when tested by the creatinine and ural levels as well as increased in superoxide dismutase making N. sativa a good chemical agent of free radicals. [69]

Clinical Data

No documentation

Poisonous Management

No documentation

Line drawing

42

Figure 1: The line drawing of N. sativa [2]

References

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